Acute and chronic pains originating from the urinary bladder are common clinical entities affecting more than 50% of females at some time in their lives. In an attempt to understand urinary bladder hypersensitivity in a translational manner, this ongoing research project has used rodents to define basic neurophysiological elements of bladder sensation at spinal and supraspinal levels. Using urinary bladder distension (UBD)-evoked reflexes and spinal/supraspinal neuronal responses as experimental endpoints, clinically-relevant models of bladder hypersensitivity have been developed. Whereas the effect of inflammation as an exacerbator of pain has been investigated, the effects of acute stress have not. The present set of studies seeks to reverse the deficit of knowledge that exists in relation to the mechanisms of acute stress as an exacerbator of urinary bladder pain by performing systematic experimental investigations in our translational model. Three Specific Aims are proposed: Specific Aim #1: To quantitatively characterize effects of acute footshock-induced stress on reflex responses to UBD in rats which experienced neonatal bladder inflammation. Specific Aim #2: To quantitatively characterize effects of acute footshock-induced stress on spinal neuronal responses to UBD in rats which experienced neonatal bladder inflammation. Specific Aim #3: To quantitatively determine the role of supraspinal mechanisms on footshock-induced alterations to responses to UBD in rats which experienced neonatal bladder inflammation. These studies will expand upon preliminary studies and will determine quantitatively the effects of the classic stressor, intermittent nonpainful footshock, on reflex (visceromotor) and spinal dorsal horn neuronal responses to UBD. Effects of descending modulatory influences will be assessed using transection of the spinal cord and/or focal supraspinal lesions in animals which experienced neonatal bladder inflammation and controls. The proposed studies examining acute stress-related effects in rodent model systems will give insight related to the effect of an acute exacerbating factor related to bladder pain. An improved understanding of sensory processing related to IC and of urinary bladder sensory pathways and their modulation by acute stress will result in an increased translation of basic science to therapeutics for bladder pain. PUBLIC HEALTH RELEVANCE: The proposed studies examining acute stress-related effects in rodent model systems will give insight related to the effect of an acute exacerbating factor related to bladder pain. Neural pathways and mechanisms related to an acute stressor - footshock - will be defined. An improved understanding of sensory processing related to IC and of urinary bladder sensory pathways and their modulation by acute stress will result in an increased translation of basic science to therapeutics for bladder pain.